ABSTRACT
Introduction: The PACIFIC trial demonstrated that a year of consolidation PD-(L)1 inhibition following concurrent chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival (OS). The optimal duration of consolidation IO therapy in this setting is undefined. Studies in metastatic NSCLC demonstrate that combination PD-(L)1/CTLA-4 inhibition improves OS over chemotherapy alone. This trial evaluated the use of combination Nivolumab (N) plus Ipilimumab (IPI) or N alone for up to 6 months in unresectable stage III NSCLC after concurrent CRT. Methods: This is a randomized phase II, multicenter trial of 105 pts with unresectable stage IIIA/IIIB NSCLC. All pts received concurrent CRT and were then enrolled and randomized 1:1 to receive N 480mg IV q4wks (Arm A) for up to 24 weeks or N 3mg/kg IV q2 wks + IPI 1mg/kg IV q6 wks (Arm B) for up to 24 weeks. The primary endpoint is 18-month PFS compared to historical controls of CRT alone for arm A (30%) and CRT followed by Durva for arm B (44%). Secondary endpoints include OS and toxicity. Results: From 9/2017 to 4/2021, 105 pts were enrolled and randomized, 54 to N alone (A) and 51 to N + IPI (B). The baseline characteristics for arm A/B: median age (65/63), male (44.4%/56.9%), stage IIIA (55.6%/56.9%), stage IIIB (44.4%/43.1%), non-squamous (57.4%/54.9%), and squamous (42.6%/45.1%). The percentage of pts completing the full treatment was 70.4% in A and 56.9% in B (p=0.15). Median f/u was 24.5 and 24.1 months on A and B, respectively. The 18-month PFS was 62.3% on A (p <0.1) and 67% on B (p <0.1), and median PFS was 25.8 months and 25.4 months, respectively. Median OS was not reached on either arm, but the 18- and 24-month OS estimates were 82.1% and 76.6% for A and 85.5% and 82.8% for B, respectively. Treatment-related adverse events (trAE) on arm A/B were 72.2%/80.4%, and grade ≥3 trAEs on arm A/B were 38.9%/52.9%. There was 1 grade 5 event in each arm (COVID19-A, Cardiac Arrest-B). The number of pts with grade ≥2 pneumonitis were 12 (22.2%) in A and 15 (29.4%) in B, with 5 (9.3%) and 8 (15.7%) grade ≥3 events, respectively. The most common (>10%) non-pneumonitis trAEs in A were fatigue (31.5%), rash (16.7%), dyspnea (14.8%), and hypothyroidism (13%), and in B were fatigue (31.4%), diarrhea (19.6%), dyspnea (19.6%), pruritus (17.7%), hypothyroidism (15.7%), rash (15.7%), arthralgia (11.8%), and nausea (11.8%). Conclusions: Following concurrent CRT for unresectable stage III NSCLC, both N and N + IPI demonstrated improved 18-month PFS compared with historical controls despite a shortened interval (6 months) of treatment. OS data are still maturing but 18- and 24-month OS estimates compare favorably to prior consolidation trials. Toxicity for N alone was similar to prior single-agent trials, and the combination of N + IPI resulted in a higher incidence of trAE’s, although consistent with prior reports. Keywords: Consolidation Immunotherapy, Stage III NSCLC